The mechanisms behind the alteration of chemical carcinogenesis by the dietary lipotropes methionine, choline and vitamin B12 have been studied. The effects of vitamin B12 deficiency on chemical carcinogenesis, of a marginally lipotrope-deficient diet on 2-acetylaminofluorene (AAF) metabolism and of diethylnitrosamine (DEN) on folate and vitamin B12 metabolism were studied in rats. Vitamin B12-deficiency appeared to slightly inhibit the carcinogenic activities of DEN towards liver and of methylnitrosonitroguanidine towards stomach; the activities of 6 other carcinogens were unaffected by the vitamin B12-deficiency. The simultaneous administration of AAF and of a lipotrope-deficient diet that increases the hepatocarcinogenic activity of AAF in male rats increased the ratio of N-hydroxy metabolites in the murine. DEN administration to rats produced a methyl-dependent folate deficiency and decreased hepatic levels of methyl-B12.